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The Homebase 10
The Homebase
10 is a simple to make wire halo antenna for 10m (28MHz) built using
parts available from the local DIY store. The resulting antenna
is very effective on 10m despite its small size and light weight.
INTRODUCTION Many will be familiar with the Cobwebb design from Steve Webb (G3TPW), which is a 14-28MHz horizontal, omni-directional, wire antenna. This works well, but it is very expensive and, in my humble opinion, it looks a bit like a rotary clothes line stuck on a pole up in the sky: my neighbours would not approve! I can make no claims for originality as this antenna takes some of the ideas from various similar concepts such as the VHF halo, the old Cushcraft Squalo, the GM3VLB delta beam and the Cobwebb. The antenna can be assembled for less than �10 and, with reasonable luck, the parts needed will be available from the junk in the back of the shed. All the parts required for this antenna may be bought from the local Homebase, B&Q or similar DIY stores. As it is designed for 28MHz (10m) then the name just had to be the Homebase 10. CONSTRUCTION The antenna consists of two main parts: (a) a wooden X skeleton section which provides the support struts and (b) a wire dipole folded into a square �halo� shape. As with the Cobwebb, the centre part of the wire dipole section is made as a folded dipole (310cms overall length split in the middle on one side for the feedpoint) which brings the feed point impedance close to 50 ohms. The remainder of each dipole leg is 105cms long added to the ends of the folded dipole section. The folded dipole is made by paralleling up two pieces of the PVC cover multi-strand wire and holding these close together with cable ties. A choke consisting of 6 turns of the coax cable about 5cms diameter close to the feed point helps to keep RF from the outer of the coax. Firstly, assemble the support strut woodwork by taking four pieces of 21 x 12 mm wood 1m long (with the 21mm side vertical) and drill two holes close to one end to line up with metal corner brace holes. The four 50mm corner braces and the drilled aluminium plate are screwed together and to the wooden struts. When screwed together, the four wooden pieces form a cross with the aluminium plate trapped between two of the corner braces and the wooden struts. Coat the wood, the assembled brackets and the nuts & bolts with three layers of outdoor yacht varnish to protect them from the elements. A better alternative may have been to use nylon rods but the rectangular wooden struts allowed a simpler mechanical arrangement.Next assemble the wire dipole. Note how the feedpoint attaches to the centre of the folded dipole section. Initially �tack� the wire onto the corners of the cross. The feed point is attached at one end of one of the cross members. This helps to provide support as this is the heaviest part because of the added weight of the coiled coaxial choke. Bring the coaxial feeder away from the feedpoint back towards the middle of the antenna along the wooden support strut. The free ends of the wires are pulled together via a thin piece of insulating nylon or polypropylene cord. Make small loops in the end of each wire to attach the cord. The losses of the material used to connect the wire ends together may be checked by putting a length of it in a powered microwave oven for 60 seconds to see how hot it gets: if it remains cool, the chosen material should be OK. TESTING AND ADJUSTMENT Connect the 28MHz rig via an SWR bridge to the antenna. Position the antenna in the air clear of other wires and metalwork. This is best done in the garden as some adjustment of the wire length may be needed. Check the SWR at the bottom, middle and top of the 28MHz band. If all is well, the match should be <1.5:1 over about 600kHz of the band. If adjustment is needed, lengthen or shorten the free ends of the wire until the lowest SWR is centred where you want to operate within the band. My version was adjusted to give a low SWR between 28-28.6MHz where most of the SSB, CW and data DX activity is found. Try to position the antenna in the clear when checking resonance each time. Adjustment should not be too critical. Once adjustments have been completed attach the antenna wire to the corners of the cross in a more permanent fashion ensuring the soldered connections joining the folded dipole section to the end wires and the feed point junction to the coax are suitably waterproofed. Joints should be covered in heat-shrink sleeving or waterproof tape. Use nylon cable ties to secure the folded dipole wires to each other, the coax choke and the coax feeder. In my version I added a small extra piece of wood joining the tops of the wooden strut supporting the feed coax and its opposite part to give this additional strength. PERFORMANCE Erect the antenna as high as you can and start collecting 28MHz DXCC countries. You now have a small, lightweight but effective, 28MHz DX antenna which should last a few years and give you plenty of fun. If anything should fail you know the whole thing can be rebuilt in a few hours for less than the price of a takeaway. A dual 10m/6m version should be easy to make too. Contacts so far suggest the antenna is working as planned with a near omni-directional radiation pattern. Despite running only 5 or 10W on SSB and CW, reports have been excellent. I've even had 4 QSOs with 599 reports into Europe when running just 50mW. The antenna does not need any matching when used over its intended part of the band, but an auto-ATU such as that in the IC703 helps to optimise the match in other parts of the band. Unexpectedly, the antenna performs pretty well on other higher HF bands too. Indeed I had contacts on 12m and 20m, matching the antenna successfully with the IC703 auto-ATU, before the 10m band opened up to allow any QSOs on 10m. Although only tested at 5-10W - the most I can run, HI - this antenna should work with full legal power as long as the losses in the support cord joining the free antenna ends are low. PARTS LISTWire (PVC insulated multi-strand) 10m total approx (including some for prototyping) All parts except the coaxial cable may be obtained from DIY stores. Coax is available from many sources including Maplin. |
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If $10 billion sounds like a lot of money, consider this: the estimated cost of a nuclear accident, according to 1982 estimates, would be as high as $590 billion per reactor. "The proposed law says contractors are not liable for one extra cent of any damages they cause, even if they are found to be negligent in the accident," said Diane D'Arrigo, radioactive-waste project director at the Washington, D.C.-based Nuclear Information and Resource Service.
8. Nuclear power is a rip-off. When all its reactors are up and running, SONGS produces only about 20 percent of SCE's energy, but every penny of SONGS' $4.3 billion construction cost has been paid for by California taxpayers, thanks to a unique deal with the California Public Utilities Commission. But that's only half the story: the public is also paying every cent of the cost of "decommissioning" the plants, which basically involves classifying each part of the reactor by radioactivity, breaking up the plant into pieces, and burying them on some Indian reservation. SCE has already started taking apart SONGS' Unit 1 reactor, but it won't be finished until 2008, and remember, there are still two more reactors to go. Because there's still no place to safely bury all this waste—see No. 3 above—the cost of decommissioning is still unknown but definitely measurable in the billions of dollars. 9. Although SONGS was designed to be operated safely for just 20 to 30 years, SCE has already extended its license to operate the plant until 2022. As the concrete-lined reactor walls get older, their ability to contain the pressure involved in containing a nuclear accident gets weaker. Think of the aging passenger jet that lost its roof 24,000 feet over Hawaii a few years back. "When the chain reaction that creates nuclear energy takes place, it embrittles the containment vessel," said PSR's Parfrey. "Then, if you ever have to cool the rods in an emergency, you will have a structure that will not be able to contain the pressure." 10. Even without the threat of terrorism, the damn thing is just too dangerous. San Onofre's environmental-impact report estimates that if a major release of radiation occurs at SONGS, here's what we can expect: 130,000 immediate fatalities, 300,000 latent cancers and 600,000 genetic effects passed on to Southern California residents and their children. Have a nice day!


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Cash Management Techniques: Discuss the concept of cash rebates and their effect on business; are they ethical?
Among the cash management techniques used by most businesses are those that slow down their bill payments. A good example for this is the concept of cash rebates. Cash rebates are most commonly offered on household items like computers and other electronics.
Research "cash rebates" and other similar cash management techniques. Answer the following questions:
Are these practices sound business decisions? Are they ethical? Explain.
What percentage of the rebates offered are actually paid?
Select a business of which you are familiar, and answer the following question:
Would you recommend that this business use cash rebates?
Solution Summary
This solution provides detailed information on cash management techniques - in particularly on rebates and why offering them may be considered a sound business practice. Information is also given to help you decide on whether such a business practice is considered ethical. An example is given in the solution for a business that you could recommend to offer rebates. This solution is approximately 1600 words.


text:
Welcome to Third Grade Reading Street Teacher Resources!
PowerPoints, downloads, and links
Third Grade Online Reading Games
A free Spelling City App is now available for iPads. Once the app is installed, click on "Find List," type user name: readingstreet3 All stories are listed in numerical order. "S" is spelling words, "V" is vocabulary words, and "OV" is other vocabulary words.
You are welcome to link to my site and use my resources in your classroom, but please respect my hard work and do not copy my page or files and add them to your website as your own work!
Password Game template was created by Connie Campbell.
Note about the Weekly PowerPoint for each story: If you wish to add to the slides with graphic organizers, you may. Just click on "end show" and type in what you wish. When you have finished, click to begin the slide show again.
All Grades:
Becky Breid
Carl's Corner
Denise Talbot's Task Cards
Everything Literacy
Falmouth Public Schools
Hill-Robert Elementary School (Cathy White)
Houlton Elementary School
K-2 Reach Resources (PPS)
Leveled Reader Leveling Guide (Portland Public Schools)
Leveled Readers
Literacy Malden Wikispace
Mitchell Elementary
Pearson SuccessNet
Printable Grammar Games
Progressive Phonics
Readability Site
Reading Street Group
Richland Parish Schools
RS Resources (Portland Public Schools)
Smart Board Goodies
SMART Exchange Reading Street Search
Smartboard Goodies (Home page)
Smartboard Goodies -list of various links of things other than Smartboard files
Spang Gang - online games
Technology-Infused Activities - Cheryl Tice
Waltke's Web (wonderful site)
Third Grade Online Resources:
Apple Orchard Printables
C. Slaughter
Catawba County Schools - Centers
Cheryl Tice
Collier Elementary Smart Board Files
Collier File Hive Wiki
Fairhope Elementary - Susan Sims
Falmouth Schools
Family Times for Third Grade
FCRR Center Activities
Florida Center for Reading Research
George Hall Elementary Wiki
Kimberly Lane's Reading Street
Malden Wikispace
Miss Hunt's 3rd Grade Resources
Morum's Forum
Mrs Thonus' Resources
Mrs. Cebula
Mrs. Thonus's Third Grade Stars
Ms. Albers
Ms. Green's Trifolds
Ms. Marquis
Ms. Marquis Resources
O'Neal's Resources
Peru Central School (Third Grade)
Peru Schools 3rd Grade Leveled Readers
Portland Public Schools
Prince's Posts
Protsman Elementary
Reaching for Our Goals - Unit 6
Reaching Our Goal Companion Website (Unit 6 only)
Richland Schools
Spelling City
Tech Toolkit Wiki (SMART Response files only)
Technology-Infused Activities
Tessa Samuel's Wikispace
Third Grade Group
Third Grade Tennessee Teachers Group
Tri-Central Elementary
V. Stauffer - Story Author Websites
Third Grade Portaportals
Portaportal - Barr
Portaportal - Chaag
Portaportal - Giles
Portaportal - Given
Portaportal - Manley
Portaportal - McCracken
Portaportal - Parrish
Portaportal - Peer
Portaportal - Rave
Portaportal - Sago
Portaportal - Stultz
Portaportal - Susan Sims
Portaportal - Thriving Third
Portaportal - Whetzel
Protaportal - Minot
Quia Sites
Organizing RS Materials
Pictures & explanation of how I organize the second grade materials.
Lesson Plans
Curriculum Guides and Alignment - Reading/Language Arts - objectives for each story matched to the Alabama Course of Study (taken from the Baldwin County, Alabama website). Scroll down and find the grade level.
Sticky Notes - Portland Public Schools
Reader Response, Vocabulary Centers
File Downloads by Units
Send the Story Words & Skills sheet home on Monday for the students to use as a study guide at home.
Print each category (spelling words, vocabulary words, other vocabulary words) of word cards on a different color of paper.
Print the definitions on white paper, cut apart, and tape together to fit into a pocketchart.
Use a Fiskar paper cutter (used for scrapbooking) to cut word cards and definitions apart.
When finished with the story, put all cards and definitions into a small manila envelop.
Unit 1
Story Words & Skills
Spelling Word Cards
Vocabulary Word Cards
Vocabulary Definitions
Other Vocabulary Word Cards
Other Vocabulary Definitions
Unit 2
Unit 3
Unit 4
Unit 5
Unit 6
Contributed by Kelly Davis:
Vocabulary Boxes - 6 words & definitions
Vocabulary Boxes - 6 words & sentences
Vocabulary Boxes - 6 words, definitions, & sentences
Spelling Words List - taken from online...if this is your work, please let me know so I can give you full credit
Skim & Scan
Contributed by Rebecca Boehler
Reading Buddy Tic-Tac-Toe
Reading Buddy Non-Fiction Tic-Tac-Toe
Contributed by Katie Cherritt
Contributed by James Pluskota:
Assessment Forms
Guidelines for Pretests
Pre-Test Letter to Parents
Third Grade Units 1-6 Pretest Scoring Sheet
Third Grade Unit 1 Pretest (Exam View installation required)
Third Grade Unit 1 Pre-Post Test Parent Form
Third Grade Unit 2 Pretest (Exam View installation required)
Third Grade Unit 2 Pre-Post Test Parent Form
Third Grade Unit 3 Pretest (Exam View installation required)
Third Grade Unit 3 Pre-Post Test Parent Form
Third Grade Unit 4 Pretest (Exam View installation required)
Third Grade Unit 4 Pre-Post Test Parent Form
Third Grade Unit 5 Pretest (Exam View installation required)
Third Grade Unit 5 Pre-Post Test Parent Form
Third Grade Unit 6 Pretest (Exam View installation required)
Third Grade Unit 6 Pre-Post Test Parent Form
Third Grade Unit Skills
Unit 1: Dollars and Sense
Story PowerPoint
Spelling City Games & Handwriting Worksheets
Password Game
Multiple Choice Spelling Test
Mrs. Hulsey's Trifolds
Tic-Tac-Toe Choice Boards
Linda Goodall's Trifold
Lori Frank's Roll and Read Games for Leveled Readers
Roll & Read (PDF)
Deborah Thonus's Story Links
Tessa Samuelson's Story Activities
Waltke's Webb:
Unit 1 Resources
Unit 2: Smart Solutions
Mrs. Hulsey's
Lori Frank's
Roll and Read Games for Leveled Readers
Unit 2 Resources
Lori Frank'
Unit 3: People and Nature
Unit 3 Resources
Spelling City Games & Handwriting Worksheet
Unit 4: One of a Kind
Unit 4 Resources
Unit 5: Cultures
Story PowerPoint (updated 1/15/11)
Unit 5 Resources
Unit 6: Freedom
Story PowerPoint (updated 1-25-11)
Unit 6 Resources
Clip Art from Phillip Martin
Home Email
Plaid Backgrounds from Snoville


text:
GradeSort Ascending and Descending by Grade | CommentsSort Ascending and Descending by Comments | PriceSort Ascending and Descending by Price | Qty | Buy Now |
Priced to sell, "BARGAIN" items are 70 to 79 percent of original condition. More than average wear for the age of the item, and may have dents, dings or finish loss. Glass may have marks or blemishes, but should not affect picture quality. |
$53.00 $49.00 |
Item Added To Cart Canon EOS POWER DRIVE BOOSTER PB-E2 (1V/1VHS,3,1/1N) Bargain / None |
Can be used with EOS-1 and EOS-1N. Raises EOS-3 top frame advance rate to 7 fps. Vertical-grip controls include, shutter button, AE lock button, Main Dial, focusing point selector and FE lock / multi-spot metering button.
Batteries - 8 AA 1.5v (Alkaline, Ni-Cd, Lithium)
Dimensions : 158.7(W) x 116.4(H) x 82.5(D) mm / 6.25(W) x 4.58(H) x 3.25(D) in
Weight : 485g / 17.1oz


text:
The WARP_TRI function returns an image array with a specified geometric correction applied. Images are warped using control (tie) points such that locations ( Xi, Yi ) are shifted to ( Xo, Yo ).
The irregular grid defined by ( Xo, Yo ) is triangulated using TRIANGULATE. Then the surfaces defined by ( Xo, Yo, Xi ) and ( Xo, Yo, Yi ) are interpolated using TRIGRID to get the locations in the input image of each pixel in the output image. Finally, INTERPOLATE is called to obtain the result. Linear interpolation is used by default. Smooth quintic interpolation is used if the QUINTIC keyword is set.
This routine is written in the IDL language. Its source code can be found in the file
in the
subdirectory of the IDL distribution.
Set this keyword equal to a 2-element vector containing the size of the output image. If omitted, the output image is the same size as Image .


text:
« Back to Article |
ASTROS NOTES: Oswalt feeling no pain after bullpen session
Oswalt feeling better after bullpen session
BRIAN McTAGGART, Copyright 2008 Houston Chronicle | July 9, 2008
Astros pitcher Roy Oswalt threw about 35 pitches in the bullpen at PNC Park on Tuesday afternoon with manager Cecil Cooper and pitching coach Dewey Robinson watching closely.
Oswalt said he was pain-free.
Oswalt hasn't pitched since June 30 because of a pain in his side, a condition caused by a worn-down disk in his back.
He had an injection into the area Saturday and will start Friday in Washington.
"I was throwing 70-80 percent when I first got out there, but the last 20 pitches I threw as hard as I could throw and didn't feel anything," Oswalt said.
Insurance in the bullpen
Righthander Chad Reineke joined the team Tuesday in Pittsburgh after being called up from Class AAA Round Rock. Reineke will make his major league debut when he gets into a game.Reineke, who was 5-8 with a 4.87 ERA in 17 starts in Round Rock, will provide insurance for the bullpen, which is still recovering from Sunday's 17-inning game in Atlanta.
"It's pretty crazy right now," said Reineke, a 13th-round draft pick in 2004. "Everything happened fast and I wasn't sure if I was activated or coming up as an emergency."
Hernandez sent down
Runelvys Hernandez admitted he was perhaps expecting to get put on waivers Tuesday, a day after he gave up 13 hits and 10 runs in four innings.But Hernandez was pleased to learn the Astros hadn't given up on him and were sending him to Class AAA Round Rock.
"It's another life," he said. "It's good. That's another wake-up (call).
"It looks like the team cares about me and I'm not going to put my head down. I'm going to go there and work hard and try to get back."
Matsui to return today
Second baseman Kaz Matsui will be activated from the 15-day disabled list for today's series finale against the Pirates, manager Cecil Cooper said.Matsui has been on the disabled list since June 23 with a strained right hamstring and has missed 30 games this year because of injuries. Cooper said he would likely go back down to 12 pitchers today.
Erstad earns playing time
Darin Erstad started in center field for the fourth time in five games Tuesday. Michael Bourn is in an 0-for-19 slump, and manager Cecil Cooper said Erstad had earned the right to play."We're going to go on a performance-type situation," Cooper said.
"If you play well you get to play, and Darin has been swinging the bat well. It's not a demotion." Cooper talked with Bourn and catcher J.R. Towles, who has lost playing time to veteran Brad Ausmus, on Tuesday to reassure them the team hadn't lost confidence in them.
"(Bourn) is still our guy, still our center fielder of the future," Cooper said. "The same thing with J.R. I told them we're trying to get jumpstarted and get some wins before the break and after the break it will be a different story."


text:
Christensen, Steven A. (2005) Order in institutional telephone talk: three observations. In: 2005 University of Southern Queensland Department of Psychology Research Colloquium, September 2005, University of Southern Queensland, Toowoomba, Australia. (Unpublished)
Christensen_2005_Research_Colloquium.pdf Download (107Kb) |
[Abstract]: In this paper I introduce some features of conversation analysis through three actions. I do this, firstly, by displaying three observations of a telephone call to a local government council. Secondly, by invoking participants' capacities, skills and resources as social interactants to analyse this call. And thirdly, by commenting on how traditional approaches to psychology might explain the orderliness of the call. I then conclude the paper with some modest claims about how the communication choices made by professionals shape the quality of service interactions, and about the potential for conversation analysis to contribute to psychological research at USQ.
Statistics for this ePrint Item |
Item Type: | Conference or Workshop Item (Commonwealth Reporting Category E) (Paper) |
Refereed: | No |
Item Status: | Live Archive |
Additional Information: | Author holds copyright. |
Depositing User: | Mr Steven Christensen |
Faculty / Department / School: | Historic - Faculty of Sciences - Department of Psychology |
Date Deposited: | 29 Aug 2008 04:35 |
Last Modified: | 02 Jul 2013 23:05 |
Uncontrolled Keywords: | conversation analysis, telephone talk, orderliness |
Fields of Research (FOR2008): | 17 Psychology and Cognitive Sciences > 1701 Psychology > 170107 Industrial and Organisational Psychology 20 Language, Communication and Culture > 2001 Communication and Media Studies > 200105 Organisational, Interpersonal and Intercultural Communication |
URI: | http://eprints.usq.edu.au/id/eprint/4339 |
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text:
Research news
The US National Academy of Sciences yesterday announced the election of 72 new members and 15 foreign associates, in a list that includes both rising stars and venerable researchers.
Vernon Ingram at the Biochemistry Department, Massachusetts Institute of Technology - sometimes referred to as the 'The Father of Molecular Medicine' for his seminal work in identifying the single amino acid mutation that causes sickle cell anemia - is elected, 53 years after receiving his PhD and 32 years after his election to the Royal Society in London. In contrast, Yale University's Jennifer Doudna, has been elected to the Academy in recognition of her work in elucidating the structure and function of ribozymes and RNA-protein complexes only 13 years on from becoming a PhD.
Also elected is Pat Brown from the Department of Biochemistry, Stanford University School of Medicine. It was his team that developed the microarray technology that has enabled meaningful analysis of the vast amounts of information generated by the numerous genome projects. In addition he is a committed proponent of freedom of access to academic research through his involvement with the Public Library of Science (PLoS).
Among the list of new foreign associates is Tomoko Ohta at the National Institute of Genetics, Japan. She has spent most of her post-doctoral career at the Institute developing the neutral theory of evolution in conjunction with Motoo Kimuri.
The seemingly ubiquitous Craig Venter is also elected this year, just as he leaves Celera, where he drove through the commercial sequencing of primarily his own genome, to rejoin The Institute for Genomic Research.
[http://www.nationalacademies.org/ ] webcite
The National Academies
[http://www4.nationalacademies.org/news.nsf/isbn/043002?OpenDocument ] webcite
72 New Members Chosen by Academy
[http://web.mit.edu/biology/www/facultyareas/facresearch/ingram.shtml ] webcite
Vernam Ingram - Biochemistry Department, MIT
[http://www.royalsoc.ac.uk/royalsoc/index.html ] webcite
The Royal Society
[http://www.csb.yale.edu/people/doudna/jad/jad.html ] webcite
Jennifer Doudna
[http://brownlab.stanford.edu/ ] webcite
Pat Brown
[http://www.publiclibraryofscience.org/ ] webcite
Public Library of Science
[http://www.nig.ac.jp/home.html ] webcite
National Institute of Genetics
[http://www.celera.com/ ] webcite
[http://www.tigr.org/ ] webcite
The Institute for Genomic Research


text:
Christine Benz: I am Christine Benz for Morningstar.com. Despite concerns about the impending fiscal cliff, stocks have actually enjoyed very nice gains so far in 2012.
Joining me to provide a recap of equity-fund performance so far this year is Shannon Zimmerman. He is associate director of fund analysis with Morningstar. Shannon, thank you so much for being here.
Shannon Zimmerman: Very good to be with you at the end of the year.
Benz: Shannon, it's been a year where the market has really lifted all boats. When we look across stock-fund performance, what we see really is double-digit gains across the board. I'm wondering, when you drill in a little bit, if you look at, say, large caps versus small caps, do you see any gradations there?
Zimmerman: It's more subtle than in some market environments where the differences between small cap and large has been quite huge. This year though--and we talked about this earlier in the year too--one pattern that has persisted is that it has been better to be bigger.
So, larger-cap funds have generally fared better than smaller-cap funds. The best-performing category in the year--and it really was kind of neck-and-neck--is mid-cap value. But the second best-performing category is large growth. And the smaller-cap diversified categories are all toward the back of the list in terms of performance year to date. But as you say [it has been] a really fine year in absolute terms. All the categories on the domestic-equity side--the diversified and the more narrowly tailored funds--are up double digits.
Benz: How about the growth-versus-value spectrum. Do you see any gradations there?
Zimmerman: Not so much, in terms of the valuation spectrum. The patterns that we saw earlier in the year where growth was trumping value, that's kind of faded away. It was subtle to begin with, and now it doesn't exist at all.
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Members of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family are known to influence development, angiogenesis, coagulation and progression of arthritis. As proteinases their substrates include the von Willebrand factor precursor and extracellular matrix components such as procollagen, hyalectans (hyaluronan-binding proteoglycans including aggrecan), decorin, fibromodulin and cartilage oligomeric matrix protein. ADAMTS levels and activities are regulated at multiple levels through the control of gene expression, mRNA splicing, protein processing and inhibition by TIMP (tissue inhibitor of metalloproteinases). A recent screen of human cartilage has shown that multiple members of the ADAMTS family may be important in connective tissue homeostasis and pathology.
ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) proteinases are a group of secreted enzymes; many of them have been found to be expressed in cartilage [1]. Functional investigations of these enzymes have largely been limited to a few specific members, particularly ADAMTS-4, which has been implicated in the progression of arthritis [2,3]. The purpose of this review is to summarise the structure, function and regulation of the entire ADAMTS group of proteinases and to emphasise areas of potential relevance with regard to the homeostasis and pathology of connective tissues.
ADAMTS evolution and structure
ADAMTS proteinases were first described in mice by Kuno and colleagues in 1997 [4] and have subsequently been identified in mammals and Caenorhabditis elegans. They form part of subfamily B (adamalysin subfamily), family M12, in clan MA of the metallopeptidases, as defined in the MEROPS database [5,6] and are structurally and evolutionarily related to the ADAM (a disintegrin and metalloproteinase; also part of the adamalysin subfamily) enzymes and, more distantly, the matrix metalloproteinase (MMP; family M10 in clan MA) enzymes. A comparison of the minimal characteristic domain organisation of these groups of proteinases is shown in Fig. 1.
Figure 1. Schematic representation of the minimal domain organisation of matrix metalloproteinase (MMP), ADAM (a disintegrin and metalloproteinase) and ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs; for example ADAMTS-4) proteinases. Note that most MMPs possess additional C-terminal extensions containing domains such as hemopexin-like and fibronectin type II domains. ADAMTS possess from 0 to 14 additional thrombospondin type 1-like repeat (TSR)-like motifs C-terminal to the spacer domain. EGF, epidermal growth factor; TM, transmembrane.
Nineteen distinct human ADAMTS gene products have been identified. A nearest-neighbour dendrogram constructed (using ClustalW 1.7 [7]) from sequence alignments of the entire protein indicates that human ADAMTS proteins can be broadly divided into four subdivisions, which also seem to share structural characteristics and activities (see Fig. 2 and below). A dendrogram constructed from the sequence alignment of the catalytic domains was almost identical, which implies that the catalytic and ancillary domains evolved together (data not shown). The first of the divisions, consisting of ADAMTS-1, -4, -5, -8, -9, -15 and -20, subdivides into two further groups, one composed of ADAMTS-9 and -20 and the other of ADAMTS-1, -4, -5, -8 and -15. A second, well-defined, subgroup contains ADAMTS-2, -3 and -14. ADAMTS-13 stands alone, and the remaining ADAMTS members form a loosely defined subgroup within which members are further divided into four pairs (ADAMTS-19 and -17, ADAMTS-18 and -16, ADAMTS-12 and -7, and ADAMTS-10 and -6) sharing structural features. A detailed study of the phylogenetic relationship of the ADAMTS family members has recently been published [8].
Figure 2. Schematic representation of the structural and evolutionary relationship of the 19 human ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) gene products. The dendrogram was calculated with ClustalW 1.7 [7]. The structural representation of ADAMTS proteins was adapted from [81]. Where applicable the long form of splice variants is shown (see the text). CS, chondroitin sulphate; CUB, complement C1r/C1s, Uegf (epidermal growth factor-related sea urchin protein) and BMP-1 (bone morphogenic protein-1); PLAC, protease and lacunin; TSR, thrombospondin I-like repeat; vWFCP, von Willebrand factor-cleaving protease.
ADAMTS domain structure
The signal sequence of ADAMTS proteins is followed by a pro-region of varying length, but which is unusually short in ADAMTS-13. The pro-domain of all ADAMTS proteinases contains at least one furin cleavage consensus motif; it is therefore generally believed that the zymogen forms of ADAMTS proteinases are cleaved intracellularly and that secreted proteins are in the mature form. This mechanism of maturation is supported by studies of ADAMTS-4, which identify an N terminus of F213ASLS in supernatants conditioned by cells transfected with ADAMTS-4, suggesting that the prodomain is efficiently removed in vivo [9]. The same study also demonstrated that purified proADAMTS-4 could be cleaved by recombinant furin in cell-free experiments. Furin has recently been shown to interact with the pro-form of ADAMTS-4 and to co-localise within the trans-Golgi network [10]. Using furin inhibitors and RNA interference techniques, the removal of the pro-domain was inhibited without affecting secretion, demonstrating an important role for furin in intracellular processing [10]. The same study also revealed the presence of furin-independent pro-domain processing pathways in some cells.
The catalytic domains of ADAMTS proteinases share a high degree of similarity and contain the zinc-binding sequence HEXXHXXGXXH, in which the catalytic zinc is coordinated by the three histidine residues. This arrangement is facilitated by the conserved glycine, which permits a tight hairpin loop and enables the third histidine to occupy its correct position [11,12]. As in all MMPs and adamalysins, the zinc-binding sequence is followed at a short distance C-terminally by a conserved methionine residue, an active-site arrangement that has been termed 'metzincin-type'. This methionine constitutes the 'Metturn', a tight turn arranged as a right-handed screw that seems to serve an important function in the structure of the active site [11].
The catalytic domain is followed by a region with 25 to 45% identity to the snake venom disintegrins, although it does not contain the cysteine arrangement of the latter [13]. This domain has therefore been termed disintegrin-like, though there is currently no published evidence that this ADAMTS domain interacts with integrins.
Unlike ADAM proteins, ADAMTS proteinases possess a well-conserved thrombospondin type 1-like repeat (TSR), homologous to the type I repeats of thrombospondins 1 and 2 [14], between the disintegrin-like and cysteine-rich domain (CRD). By analogy to thrombospondins 1 and 2 [15], the central TSR of ADAMTS proteinases is believed to function as a sulphated glycosaminoglycan-binding domain. The independently expressed central TSR of murine ADAMTS-1 required 0.46 to 0.66 M NaCl for elution from a heparin affinity column, indicating that this motif forms a functional heparin-binding unit [16].
The CRD is a well-conserved cysteine-rich sequence containing 10 cysteine residues. In contrast to ADAM proteins, in which the CRD is followed by epidermal growth factor (EGF)-like repeats, a transmembrane domain and C-terminal cytosolic region, all ADAMTS proteinases possess instead a cysteine-free 'spacer' region. This domain varies in length and contains several conserved hydrophobic residues in the N-terminal portion and an extremely variable C-terminal portion. The expression of various domain-deletion constructs of murine ADAMTS-1 revealed the CRD-spacer sequence as a functional extracellular matrix (ECM)-binding domain [16]. This role was supported by investigation of C-terminally processed forms of human ADAMTS-4, which, in combination with a deletion construct lacking the CRD-spacer sequence, indicated that these domains also bind to both heparin and the glycosaminoglycans of aggrecan (predominantly keratan and chondroitin sulphates) [9]. Three putative heparin-binding sequences were identified within the CRD-spacer sequence of ADAMTS-4, one within the CRD and two within the spacer, and peptides corresponding to these sequences were shown to inhibit the binding of ADAMTS-4 to heparin [9].
With the exception of ADAMTS-4, which terminates after the spacer region, all ADAMTS proteinases possess between 1 and 14 TSRs C-terminal to the spacer region (Fig. 2). The sequence of these additional TSRs is more variable between the ADAMTS proteinases than is the central TSR, but the independent expression of the C-terminal TSRs of murine ADAMTS-1 has indicated that these motifs can form functional heparin-binding units [16]. The TSRs of the C-terminal region are arranged in one, two or three tandem arrays. Between arrays is either a short linker sequence (ADAMTS-9 and ADAMTS-20) or a mucin-like domain (ADAMTS-7 and ADAMTS-12) [17].
Four additional types of module have been described in the ADAMTS group and all are present C-terminal to the TSR arrays. ADAMTS-9 and -20 contain a unique module, also found in the C. elegans ADAMTS GON-1, containing 10 conserved cysteine residues [18]. Several ADAMTS proteinases (-6, -7, -10, -12, -16, -17, -18 and -19) possess a PLAC (protease and lacunin) domain containing six conserved cysteine residues, which is found in some pro-protein convertases [19]. A C-terminal extension containing a unique embedded PLAC domain is present in ADAMTS-2, -3 and -14. Finally, CUB (complement C1r/C1s, Uegf (EGF-related sea urchin protein) and BMP-1 (bone morphogenic protein-1)) domains are present at the C terminus of ADAMTS-13 [20]. This domain is also present in spermadhesins, tumour necrosis factor-stimulated gene-6 and the complement proteins C1r, C1s and mannan-binding lectin-associated serine proteinases, among others [21], and there is evidence to suggest that these domains mediate protein-protein interactions with other CUB domain-containing proteins [22,23].
Functions of ADAMTS proteins
Hyalectanases: ADAMTS-1, -4, -5, -8, -9, -15 and -20
ADAMTS-1, -4, -5, -8 -9 and -15 cleave the hyalectan (hyaluronan-binding proteoglycan) aggrecan between a glutamate in the P1 pocket and small aliphatic residues in P1' (using the terminology of Schechter and Berger [24]), an activity that has previously been identified and termed 'aggrecanase' [25]. Several of these ADAMTS proteinases also cleave the related hyalectan versican at analogous sites and ADAMTS-4 has been demonstrated to cleave a further hyalectan, brevican [26]. These ADAMTS proteinases may therefore be termed 'hyalectanases'. ADAMTS-4 has recently been shown to cleave COMP (cartilage oligomeric matrix protein) as well as fibromodulin and decorin, indicating that this subgroup of proteinases is not restricted to the cleavage of proteglycans and might have a wider proteolytic spectrum [27]. There are no published reports of hyalectanase activity for ADAMTS-20, but the catalytic domain of this proteinase has been demonstrated to be proteolytically active [28].
Although aggrecan is also processed by additional proteinases, aggrecanase-mediated cleavage is a characteristic event in the catabolism of cartilage aggrecan in the arthritides [29-31]. The potential importance of aggrecanase-mediated degradation of aggrecan in cartilage, particularly with regard to the development of arthritis, is highlighted by the report that aggrecan protects collagen fibrils from degradation by collagenases [32]. Aggrecanase-mediated cleavages of aggrecan and versican have also been reported to occur in the tensile regions of tendon, suggesting that such activities might be important in the homeostasis of this tissue [33].
The involvement of ADAMTS proteinases in connective tissue turnover has been demonstrated using both cleavage-epitope-specific antibodies and inhibitors that exclude the involvement of other proteinases, particularly the MMPs [3,32]. ADAMTS-4 and -5 have been implicated as the aggrecanases involved in aggrecan degradation in osteoarthritis (OA) on the basis of mRNA and protein expression [3]. Investigations into the relative contributions of ADAMTS-4 and -5 to the aggrecanase-mediated degradation of cartilage aggrecan in arthritis models have recently been conducted in mice with the use of catalytic domain knockouts of each gene [34-36]. Both ADAMTS-4 and -5 knockout mice were phenotypically normal and indistinguishable from wild-type littermates, indicating that each enzyme was dispensable for normal development [34-36]. In a surgically induced OA model there was a significant reduction in the severity of induced OA in ADAMTS-5 knockout mice but no difference in progression or severity in ADAMTS-4 knockout mice [34,35]. Similarly, in a model of inflammatory arthritis, ADAMTS-5, but not ADAMTS-4, knockout mice were protected against aggrecan loss [36]. Furthermore, aggrecanase activity was inducible in articular cartilage explants from wild-type and ADAMTS-4 knockout mice but not from ADAMTS-5 knockout littermates [34-36]. Together these studies suggest that, at least in these mouse models, ADAMTS-5 is primarily responsible for the increased aggrecanase activity.
In addition to proteoglycan cleavage, members of this subgroup may also regulate angiogenesis. Vascularisation is a feature of both chronic tendon pathology [37] and arthritis [38], and specific ADAMTS proteins may have a role in its regulation. ADAMTS-1 and -8 possess a potent angioinhibitory activity, suppressing both fibroblast growth factor-2 and vascular endothelial growth factor (VEGF)-mediated angiogenic effects on endothelial cells but not on smooth muscle cells or fibroblasts [39]. An upregulation of ADAMTS-4 mRNA expression has also been reported in an in vitro model of angiogenesis [40]. ADAMTS-1 has been shown to interact with VEGF165 but does not cleave the growth factor, suggesting that the inhibitory effect is brought about by sequestering VEGF from its cell receptor [41]. By analogy to the thrombospondins, the angioinhibitory activity might be assumed to be mediated through the TSR motifs [42], but an ADAMTS-1 C-terminal construct consisting of the central TSR, CRD, spacer region and C-terminal TSRs was an ineffective inhibitor in a functional angiogenesis assay [43]. Furthermore, an ADAMTS-1 active site mutant displayed no angioinhibitory activity [43], therefore suggesting that both the metalloproteinase and ancillary domains are necessary in bringing about the angioinhibitory effects.
There is increasing evidence that members of this ADAMTS subgroup have roles in development. The C. elegans ADAMTS, GON-1, which is most closely related to ADAMTS-9 and -20, is involved in cell migration during the development of the gonad [18,44,45]. Studies in mice indicate that ADAMTS-20 is required for the migration of melanoblasts during embryogenesis, and that mutation of ADAMTS-20 causes a white-spotting mutation, Belted [46]. ADAMTS-1-null mice display several developmental abnormalities, primarily within the urogenital systems, affecting normal growth, organ morphology and function, and female fertility [47,48]. A role for ADAMTS-1 in ovulation has been inferred from studies in rats [49], mice [50] and horses [51], which indicate that upregulation of ADAMTS-1 mRNA correlates temporally with the appearance of ADAMTS-cleaved versican within the ECM of the cumulus oocyte complex [52]. The active form of ADAMTS-4 (but not ADAMTS-5) has been reported to co-localise with ADAMTS-mediated aggrecan cleavage in developing long bones in the rat, implying that ADAMTS-4 mediates the developmental turnover of aggrecan during long bone formation [53]. However, an ADAMTS-4 knockout mouse showed no signs of skeletal abnormalities despite evidence of ADAMTS-4 expression and activity in the growth plates of wild-type mice [34].
Procollagen N-propeptidases: ADAMTS-2, -3 and -14
ADAMTS-2 cleaves the amino peptides of type I, type II and type III procollagens [54,55], and genetic analysis has indicated that mutations in the ADAMTS2 gene correlate with the incidence of both Ehlers–Danlos syndrome type VII C and dermatosparaxis in cattle [56]. Ehlers–Danlos syndrome is a recessively inherited connective-tissue disorder that arises as a result of incorrectly processed procollagen N-telopeptides and is characterised by extreme skin fragility, joint laxity and droopy skin [57]. adamts2 knockout mice seem normal at birth but soon develop fragile skin, and male mice are infertile with decreased testicular sperm, suggesting that ADAMTS-2 has important functions both in regulating the formation and structure of skin and in the maturation of spermatogonia [58]. Despite these abnormalities, a large fraction of both type I N-propeptides in skin and type II N-propeptides in cartilage are cleaved in adamts2 knockout mice, indicating the presence of additional procollagen N-peptidases. ADAMTS-3 has since been identified as a type II procollagen N-propeptidase, whose expression is much lower than ADAMTS-2 in skin but is about 5-fold that of ADAMTS-2 in cartilage [59]. It has been suggested that the relative expression patterns of ADAMTS-2 and -3 explain the relative sparing of tissues such as cartilage in dermatosparaxis [59]. ADAMTS-14 has been identified as a homologue of ADAMTS-2, functioning as the major type I procollagen N-propeptidase activity in tendon [60].
Von Willebrand factor-cleaving protease: ADAMTS-13
ADAMTS-13 cleaves the large multimeric von Willebrand factor (vWF) precursor to generate vWF of optimal size for proper coagulation [20,61,62]. Mutations in ADAMTS-13 correlate with the occurrence of the hereditary form [63], and autoantibodies against ADAMTS-13 with the sporadic form [64], of thrombotic thrombocytopenic purpura, a disease in which the cleavage of vWF is decreased resulting in large vWF multimers.
Other ADAMTS proteins: ADAMTS-6, -7, -10, -12, -16, -17, -18 and -19
Functions have not been assigned to this subgroup of ADAMTS proteins. However, ADAMTS-7, -10 and -12 are known to be proteolytically active, although ADAMTS-7 does not cleave aggrecan or versican at the sites characteristic of the hyalectanase ADAMTS subgroup [17,65,66]. The long form of ADAMTS-7 contains both O-linked glycosylations and an N-linked chondroitin sulphate (CS) chain within its mucin-like domain [17]. The presence of this CS chain is reported to reduce the affinity of the protein for heparin [17]. Null mutations of the ADAMTS10 gene have recently been attributed to a recessive form of Weill-Marchesani syndrome, whose symptoms include short stature, brachydactyly, joint stiffness and eye lens abnormalities [67].
Regulation of ADAMTS expression, structure and activity
Regulation of expression
ADAMTS-1 was initially identified as a novel murine cDNA expressed in a cachexigenic adenocarcinoma cell line that could be upregulated by IL-1 [4]. The intravenous administration of lipopolysaccharide into mice induces expression in the kidney and heart, suggesting that ADAMTS-1 is an inflammation-associated gene product [4]. ADAMTS-1, -6 and -9 mRNA levels are upregulated in response to tumour necrosis factor-α in retinal pigment epithelium-derived cells [68] and ADAMTS-4 mRNA expression is increased by IL-17 in articular chondrocytes [69], indicating that other ADAMTS proteins might also be upregulated by inflammatory cytokines. The induction of ADAMTS-4 mRNA in β-amyloid-treated rat astrocytes supports an inflammatory-associated role for this gene [70].
In articular cartilage an upregulation in mRNA level by transforming growth factor β has been shown for ADAMTS-4 but not ADAMTS-5 [71], indicating that gene expression of these aggrecanases might be differentially regulated. Differential regulation of these genes has also been reported with an immortalised human chondrocyte cell line, in which IL-1α together with oncostatin M, but not either cytokine alone, upregulated ADAMTS-4 mRNA, whereas ADAMTS-5 mRNA was upregulated by IL-1α and there was no effect of oncostatin M [72]. An induction by IL-1α of both ADAMTS-4 and -5 in mouse cartilage explants has been reported [36]. However, studies in human articular cartilage and bovine nasal cartilage and synovium suggest that the expression of ADAMTS-4 and -5 mRNA is relatively insensitive to retinoic acid or IL-1α, despite the marked upregulation of aggrecanase activity [73-75]. A recent study of ADAMTS-4 suggests that the increase in aggrecanase activity observed after treatment with IL-1α is mediated, at least in part, through the upregulation of other enzymes that then process and activate existing ADAMTS enzyme within the tissue (see also below) [76].
Post-transcriptional regulation
Post-transcriptional regulation through alternative splicing has been identified for several of the ADAMTS proteins, including ADAMTS-6, -7 and -9 [68,77]. Initial reports predicted that ADAMTS-6 and -7 proteins would terminate after a single C-terminal TSR [78] and that ADAMTS-9 would terminate after three C-terminal TSRs [79,80]. However, the full coding sequences of ADAMTS-6, -7 and -9 are now believed to encode four C-terminal TSRs followed by a PLAC domain, seven C-terminal TSRs interrupted by a mucin-like domain and followed by a PLAC domain, and 14 C-terminal TSRs, respectively [81] (Fig. 2). In addition, other splice variants of ADAMTS-6 have been identified that terminate after the pro-domain and immediately after the catalytic domain [77]. The identification of spliced variants of ADAMTS-6, -7 and -9 suggests that splicing might be an important mechanism of regulation of this family of enzymes in which the ancillary domains of the proteins are altered. It is worth noting that the full coding sequences of ADAMTS-16 and -18 are also predicted to be longer than initially reported [80], each encoding five C-terminal TSRs followed by a PLAC domain [81].
Present studies of ADAMTS-6 have identified a potential translational regulatory mechanism for the expression of this protein [77]. The full 5' untranslated region of this mRNA contains multiple upstream ATG initiation codons followed by very short open reading frames that are predicted to recruit ribosomes to non-productive sites, thereby reducing the rate of translation. By switching to a transcript lacking these upstream ATGs, either by mRNA processing or through the use of an alternative promoter, protein production could be increased, a form of regulation that has been implicated in several diseases [82].
Post-translational regulation
ADAMTS enzymes are synthesised as zymogens that undergo the constitutive removal of the pro-domain in the secretory pathway by pro-protein convertases such as furin (see above). Secreted ADAMTS proteinases can undergo additional processing at their C-terminal end. Studies of ADAMTS-1 and -4 have identified cleavages within the respective spacer domains, and a study of ADAMTS-12 revealed a cleavage within the mucin-like domain that released the C-terminal TSR quadruplet [83]. For ADAMTS-4, two such events have been identified so far, one resulting in the removal of most of the spacer region, the other in the removal of the spacer region and most of the CRD [9]. Although C-terminal processing of ADAMTS-4 has been shown to occur through an autocatalytic mechanism [9], cell-based experiments have suggested that such cleavages are mediated by MMP [83-85]. A processing pathway in which the full-length mature enzyme is bound at the cell surface and cleaved to generate both identified truncated forms by membrane-type 4-MMP (MT4-MMP, also termed MMP-17) has been proposed [85]. The processed form retaining the CRD seems to be maintained at the cell surface by syndecan-1 through interactions with both CS and heparan sulphate chains, whereas the shortest form is released into the medium.
The cleavage of ADAMTS-1 and -4 proteins within the CRD-spacer region reduces the affinity of both for heparin, suggesting that the spacer region influences these interactions [83,84]. These processing events also alter the activities of these proteins; for example, they reduce the angioinibitory capacity of ADAMTS-1 and alter the activity of ADAMTS-4 against aggrecan [83,84]. The processed ADAMTS-4 is able to cleave aggrecan within the interglobular domain (IGD) in addition to sites within the CS attachment region that are also cleaved by the full-length proteinase [83,84]. Similarly, investigations of ADAMTS-13 proteins revealed that the major epitopes of inhibitory autoantibodies from patients with thrombotic thrombocytopenic purpura reside within the CRD-spacer region and that removal of the CRD-spacer region results in a marked reduction in vWF cleaving activity [86]. It therefore seems that the CRD-spacer region influences the activities of the catalytic domains of the ADAMTS proteinases.
Studies of ADAMTS-4 have given an insight into the influence of the ancillary domains on the proteinase activities. A recent study of truncated recombinant forms of ADAMTS-4 indicated that the presence of the CRD was required for maximal aggrecanase activity, whereas the inclusion of the spacer region prevented cleavage of aggrecan at the IGD site [27]. In addition, the presence of the spacer region prevented the cleavage of non-proteoglycan substrates such as deglycosylated aggrecan, chemically modified transferrin, and fibromodulin, an activity that required only the catalytic and disintegrin-like domains [27].
These data suggest the ADAMTS-4 catalytic domain possesses a proteolytic activity that is modulated by the spacer region so that the characteristic non-IGD 'aggrecanase' sites of aggrecan are favoured over the IGD 'aggrecanase' site and non-hyalectan substrates. In addition, the requirement of the CRD for optimal cleavage of glycosylated aggrecan compared with its negligible influences on the cleavage of non-proteoglycan substrates suggests that this domain promotes hyalectan cleavage by mediating interactions with sulphated glycosaminoglycan, in a similar manner to that proposed for the activation by heparan sulphate of growth-factor-receptor signalling [87].
The processing of ADAMTS enzymes is likely to be of importance in pathologies such as the arthritides, in which loss of aggrecan seems to be a primary event [88]. The activity of the full-length ADAMTS-4 seems to be restricted to cleavages within the CS region of aggrecan, events that would truncate the proteoglycan but would not be expected to remove aggrecan from cartilage. However, processing events removing the spacer region might generate a more promiscuous and destructive activity capable of disaggregating aggrecan–hyaluronan complexes through IGD proteolysis, resulting in the loss of aggrecan from the tissue. Additional processing, removing the CRD, may reduce activity towards aggrecan in favour of non-proteoglycan substrates. When considering the role of ADAMTS-4 or other ADAMTS proteinases in arthritic pathologies it may therefore be prudent to consider the enzyme form in addition to the absolute levels of the protein.
Regulation by inhibitors
The most significant endogenous ECM inhibitor of ADAMTS proteinases to be identified is tissue inhibitor of metalloproteinases-3 (TIMP-3) [89], although other TIMP members possess a limited inhibitory capacity [90]. TIMP-3 is unique among the TIMP family in that it binds tightly to, and is found exclusively within, the ECM [91]. In addition to the TIMP family, papilin, a protein with homology to the ancillary domains of ADAMTS proteins, is a non-competitive inhibitor of ADAMTS-2 [92]. Recently, the C-terminal portion of fibronectin has also been reported as a potent inhibitor of ADAMTS-4 [93].
Roles of the ADAMTS family in connective tissues
There have been few comprehensive studies of ADAMTS in connective tissues. However, the expression of the entire ADAMTS subfamily was recently investigated in normal and OA cartilage [1]. This study indicated that, with the exception of ADAMTS-7 and -8, normal cartilage expressed the entire ADAMTS subfamily. The most highly expressed of the ADAMTS proteinase mRNAs were those for ADAMTS-1, -5, -6, -15, -18 and -19, and observed differences between normal and late-stage OA cartilage included the lower expression of 'hyalectanase' ADAMTS proteinases (ADAMTS-1, -5, -9 and -15) and a higher expression of procollagen peptidases (ADAMTS-2 and -14). Furthermore, two ADAMTS members of unknown function (ADAMTS-12 and -16) were more highly expressed in OA. Although the levels of hyalectanases were not increased in late-stage OA this result does not preclude a role for this proteinase in the early stages of OA. In a comparison of normal and chronic painful tendon by this group (GC Jones, AN Corps, CJ Pennington, IM Clark, DR Edwards, MM Bradley, BC Hazleman, GP Riley, unpublished work), the expression of all 19 ADAMTS genes was detected. A lower expression level of ADAMTS-5 and higher levels of ADAMTS-2, -12, -14 and -17 were observed in chronic painful tendon. These data suggest that many members of the ADAMTS subfamily might possess important roles in both the homeostasis and pathology of connective tissues and are worthy of further investigation.
The ADAMTS enzymes are a group of secreted proteinases possessing a conserved N-terminal domain architecture followed by a variable C terminus. The phylogenetic relationship of these proteinases broadly defines four subdivisions, which also seem to discriminate protein activities. Evidence suggests that the synthesis of these proteinases is regulated at the level of both expression and translation and that their structures and activities are regulated through mRNA splicing and post-translationally through protein processing and endogenous inhibitors. The cleavage state of individual ADAMTS proteinases seems to be of importance, because ancillary domains (particularly the CRD and spacer region) seem to modulate the specificity of their activities, an event that might be of significance in arthritis [75]. The complex nature of the regulation of these proteinases implies that a precise control of their activities is required for the maintenance of homeostasis. A broad spectrum of ADAMTS proteinases are expressed in both cartilage and tendon, which suggests that multiple ADAMTS proteinases are important in the homeostasis of these tissues.
In conclusion, the ADAMTS proteins are complex, multi-domain, proteinases whose synthesis and activity are subjected to multiple levels of regulation and which are widely expressed in connective tissues, in both health and pathology.
ADAM = a disintegrin and metalloproteinase; ADAMTS = a disintegrin and metalloproteinase with thrombospondin motifs; CRD = cysteine-rich domain; CS = chondroitin sulphate; CUB = complement C1r/C1s, Uegf (EGF-related sea urchin protein) and BMP-1 (bone morphogenic protein-1); ECM = extracellular matrix; EGF = epidermal growth factor; IGD = interglobular domain; IL = interleukin; MMP = matrix metalloproteinase; OA = osteoarthritis; PLAC = protease and lacunin; TIMP = tissue inhibitor of metalloproteinases; TSR = thrombospondin type 1-like repeat; VEGF = vascular endothelial growth factor; vWF = von Willebrand factor.
Competing interests
The author(s) declare that they have no competing interests.
The authors wish to thank Tony Corps and Norman McKie for helpful discussion of this manuscript. GCJ is supported by The Isaac Newton Trust, The Rosetrees Trust and Cambridge Arthritis Research Endeavour.
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text:
This property has been removed by the agent. It may be sold or temporarily removed from the market
5 bedroom house for sale
The Old Coach House, Whitchurch Road, Prees, WhitchurchOffers in Region of £349,950
Property Description
Key features
- Spacious Detached House
- Five Beds, One En Suite
- Two Reception And Office
- Dining Kitchen Utility Wc
- Abundance Of Character
- Garage, Off Road Parking
- Large Gardens At Rear
- Situated In Private Lane
Full description
THE OLD COACH HOUSE IS A SPACIOUS FIVE BEDROOM DETACHED PROPERTY WITH AN ABUNDANCE OF ORIGINAL CHARACTER HAVING PLANNING PERMISSION FOR THE ERECTION OF A TWO-STOREY EXTENSION . The accommodation, which has oil fired central heating, comprises ENTRANCE VESTIBULE, LIVING ROOM having exposed ceiling and wall timbers, brick open coal fireplace, stairs to first floor and Office leading off. The LOUNGE is a lovely room having exposed ceiling timbers and a feature Inglenook brick fireplace LPG Stove and double doors to the Conservatory. DINING KITCHEN having exposed ceiling timbers and exposed wood flooring, built in units together with an oil fired Aga.
The Old Coach House
There is a side entrance/ utility area which leads to a Cloakroom. Large first floor landing; Five Bedrooms one having en suite shower; Attractive Bathroom with a contemporary white suite. There is a Garage together with parking spaces for a maximum of three vehicles, outbuilding, wood-store, gates lead to the large enclosed rear garden including orchard.
The property is situated in a private lane leading to this and three other properties. The village of Prees has facilities for daily requirements including nursery & primary school, Church, shops, doctor's dispensing surgery and recreational facilities. The North Shropshire market towns of Whitchurch, Wem and Market Drayton are between 5 to 8 miles
Entrance Vestibule
4.88m(16'0'') x 2.36m(7'9'') maximum
Door and two windows to the front, tiled flooring, door into
Dining (Living) Room
5.72m(18'9'') x 5.64m(18'6'')
Exposed ceiling and wall timbers, brick fireplace with brick hearth and wooden beam mantle, stairs to first floor, door into
2.92m(9'7'') x 1.68m(5'6'')
5.77m(18'11'') 12'3 x 5.79m(19'0'')
Exposed ceiling timbers, feature Inglenook brick fireplace with LPG Stove, double doors to
Large Shaped Conservatory
4.85m(15'11'') maximum x 5.18m(17'0'') maximum
Dining Kitchen
5.66m(18'7'') x 3.94m(12'11'')
Brick fireplace housing oil fired Aga, range of base and wall units, built in oven with cupboards above and beneath, ceramic hob with extractor over, built in fridge/freezer, inset sink unit, plumbing for dishwasher. Having exposed ceiling timbers and some exposed wall timbers, exposed wood flooring
Side Entrance/ Utility
3.15m(10'4'') maximum x 1.73m(5'8'') maximum
Built in wall cabinets, tiled worktop, plumbing for washing machine, tiled flooring
Modern WC and hand basin
Large Landing
Built in airing cupboard. Access to loft spaces. Windows overlooking rear garden.
Bedroom One
3.91m(12'10'') x 3.58m(11'9'')
Double glazed window overlooking rear garden
En Suite
2.74m(9'0'') x 1.75m(5'9'')
Modern white suite comprising panelled bath with mixer tap shower attachment, WC and hand basin, window to rear
Bedroom Two
5.66m(18'7'') x 3.99m(13'1'')
Windows to front and side
Bedroom Three
3.15m(10'4'') maximum x 2.44m(8'0'') maximum
Window to front
Bedroom Four
3.18m(10'5'') x 3.15m(10'4'')
Double glazed window to side
Bedroom Five
2.41m(7'11'') x 2.08m(6'10'')
Window to rear, some exposed wall timbers
Attractive Bathroom
2.92m(9'7'') maximum x 2.79m(9'2'') maximum
Contemporary white suite comprising freestanding shaped bath, hand basin with cupboard beneath, walk in Shower Cubicle with tiled wall surrounds, WC, inset lighting
Floor Plan
Not to scale
The Old Coach House is approached over a private drive shared with 3 neighbouring properties and this will be confirmed by solicitors during pre contract enquiries. Standing to the front of the property are parking facilities for three motor-cars together with
5.13m(16'10'') x 2.44m(8'0'')
Double doors to front
Double gates lead to the extremely spacious rear gardens laid mainly to lawn with various established shrubs including small orchard. Woodstore. Oil Tank.
5.64m(18'6'') x 3.23m(10'7'')
Housing oil fired boiler
Eer And Eir Graphs
Agents Note
Full Permission has been granted by Shropshire Council for the erection of a two-storey extension to the rear elevation. Reference 11/05534/FUL
We are advised that the property is Freehold, and this will be confirmed by the Vendor's Solicitors during pre-contract enquiries. Vacant Possession upon Completion.
Local Authority
Shropshire Council, Shirehall, Abbey Foregate, Shrewsbury, SY2 6ND. Council Tax Enquiries Revenue & Benefits 0345 678 9002/ Main Switchboard 0345 678 9000
We are advised that main electricity, water and drainage are available. Barbers have not tested any apparatus, equipment, fittings, etc., or services to this property so cannot confirm that they are in working order or fit for the purpose. A buyer is recommended to obtain confirmation from their Surveyor or Solicitor.
Disclaimer Property Details
'Property Mis-descriptions Act' - for clarification we wish to inform prospective purchasers that we have prepared these sales details as a general guide. We have not carried out a detailed survey nor tested the services, appliances and specific fittings. Room sizes should not be relied upon for carpets and furnishings. The measurements given are approximate.
Viewing & Premarketing
By arrangement with the Agents Office at 34 High Street, Whitchurch, Shropshire, SY13 1BB. Tel: 01948 667272, Fax: 01948 663951 or email: email@example.com
How To Find The Property
Travel into Whitchurch Road in Prees; The Old Coach House is situated on a private lane on the left hand side just before the cross-roads (opposite Tudor House) and The Old Coach House stands on the left hand side.
Method Of Sale
For Sale by Private Treaty.
Measurements given are approximate
Barbers for themselves and for the Vendors or Lessors of this property, whose agents they are, give notice that these particulars are produced in good faith, and set out as a general guide and do not constitute any part of the contract. No person in the employment of Barbers has any authority to make or give any representations or warranty whatsoever in relation to this property.
More information from this agent
To view this media, please visit the on-line version of this page at www.rightmove.co.uk/property-for-sale/property-17291013.html
Energy Performance Certificate (EPC) graphs
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To view this property or request more details, contact:
How much will it cost me to call the number displayed on the site?
Standard geographic charges from landlines and mobiles apply and calls may be included in your telecom provider's call package.
To view this property or request more details, contact:
How much will it cost me to call the number displayed on the site?
Standard geographic charges from landlines and mobiles apply and calls may be included in your telecom provider's call package.
Street view
To view this property or request more details, contact:
How much will it cost me to call the number displayed on the site?
Standard geographic charges from landlines and mobiles apply and calls may be included in your telecom provider's call package.
Market Info
Disclaimer - Property reference 527677A_27677. The information displayed about this property comprises a property advertisement. Rightmove.co.uk makes no warranty as to the accuracy or completeness of the advertisement or any linked or associated information, and Rightmove has no control over the content. This property advertisement does not constitute property particulars. The information is provided and maintained by Barbers, Whitchurch. Please contact the selling agent or developer directly to obtain any information which may be available under the terms of The Energy Performance of Buildings (Certificates and Inspections) (England and Wales) Regulations 2007 or the Home Report if in relation to a residential property in Scotland.